The second-to-fourth-digit (2D:4D) ratio is widely accepted as a biomarker for the degree of prenatal androgen exposure (PAE), the primary factor responsible for fetal masculinization. Studies suggest that increased PAE in females may attenuate the risk for anxiety and related disorders later in life. We hypothesize that the organizational effects of PAE on the brain may extend to the hypothalamic-pituitary-adrenal (HPA) axis. This study assessed the relationship between 2D:4D ratio and HPA-axis reactivity, as measured by plasma cortisol response to a standardized stressor. Blood samples obtained from 3-to-4-month-old infant rhesus macaques (N=268; 180 females, 88 males) during a mother-infant separation stressor were assayed for concentrations of plasma cortisol. One-to-17 years later (M=6.7 years), subject’s 2D:4D ratios were measured. Using sex as the independent variable (IV) and cortisol concentrations as the dependent variable (DV), results from a one-way ANOVA showed that infant females exhibited higher plasma cortisol concentrations, when compared to infant males (p<0.0001). Controlling for age at cortisol sampling, results from linear regressions, with 2D:4D ratio as the IV and stress-induced plasma cortisol levels as the DV, showed that female rhesus monkeys with a more masculinized 2D:4D pattern exhibited lower plasma cortisol, with no effect in males. Results suggest that PAE may attenuate HPA-axis response to stressors, suggesting that PAE has organizational effects on the HPA-axis that reduces risk for anxiety in females.